Lampen et al., Arch. Biochem. Biophys. 13, 33 (1947) and Sourkes and Trano Arch. Biochem. Biophys. 42, 321 (1953) reported in vivo experiments that suggested the presence of an enzyme system in E. coli that converts free methionine sulfoxide (MetSO) to methionine. These reports were confirmed by Ejiri et al. in two recent publications, J. Bact. 139, 161 (1979) and Anal. Biochem. 102, 393 (1980).
A similar reaction was first described in yeast by Black et al. J. Biol. Chem. 235,2910 (1960) who showed that three protein factors were required. These protein factors were later shown to be thioredoxin, thioredoxin reductase and the enzyme directly responsible for the reduction of MetSO. A MetSO reducing system has also been found to be present in animal tissues and plants.
There are a number of proteins whose biological activity is destroyed upon oxidation of methionine residues to MetSO and it is known that a wide variety of oxidizing agents produced in tissues can oxidize protein bound methionine. Although the deleterious effect of those oxidizing agents would be expected to be neutralized by various cellular enzymes (e.g. catalase, peroxidase, superoxide, dismutase), it is apparent that the efficiency of these systems is not sufficient to preclude some oxidation of methionine residues in proteins. For proteins with slow turnover, this oxidation could be crucial if methionine residues are involved in the function of the protein.
It is known, for example, that alpha-1-proteinase inhibitor (.alpha.-1-PI), which is a major serine endopeptidase inhibitor in plasma, is inactivated when exposed to oxidizing agents which cause the oxidation of specific methionine residues to MetSO. Furthermore it has been found that .alpha.-1-PI isolated from human rheumatoid synovial fluid is inactive and contains MetSO residues near its reactive center [Pong and Travis, Biochem. Biophys. Res. Comm. 96, 1449-1454 (1980)]. The inactivation of .alpha.-1-PI, as by oxidants in cigarette smoke [Science 206, 1315-1316 (1979)], results in an increased elastase activity which is responsible for the loss of lung function in emphysema. It is also known for instance that the difference between normal and cataractous lens proteins in the high level of MetSO residues in the cataractous lens protein.